scholarly journals Network-Based Analysis of OMICs Data to Understand the HIV-Host Interaction

2020 ◽  
Author(s):  
Sergey Ivanov ◽  
Alexey Lagunin ◽  
Dmitry Filimonov ◽  
Olga Tarasova
Keyword(s):  
Life Cycle ◽  
Defense Mechanisms ◽  
Human Protein ◽  
Viral Escape ◽  
Molecular Networks ◽  
Omics Data ◽  
Cd4 Cells ◽  
Host Interaction ◽  
Subtype B ◽  
Hiv 1

The interaction of human immunodeficiency virus with human cells is responsible for all stages of the viral life cycle, from the infection of CD4+ cells to reverse transcription, integration, and the assembly of new viral particles. To date, a large amount of OMICs data as well as information from functional genomics screenings regarding the HIV-1-host interaction has been accumulated in the literature and in public databases. We processed databases containing HIV-host interactions and found 2910 HIV-1-human protein-protein interactions, mostly related to viral group M subtype B, 137 interactions between human and HIV-1 coding and non-coding RNAs, essential for viral lifecycle and cell defense mechanisms, 232 transcriptomics, 27 proteomics, and 34 epigenomics HIV-related experiments. Numerous studies regarding network-based analysis of corresponding OMICs data have been published in recent years. We overview various types of molecular networks, which can be created using OMICs data, including HIV-human protein-protein interaction networks, co-expression networks, gene regulatory and signaling networks, and approaches for the analysis of their topology and dynamics. The network-based analysis can be used to determine the critical pathways and key proteins involved in the HIV life cycle, cellular and immune responses to infection, viral escape from host defense mechanisms, and mechanisms mediating different susceptibility of humans to infection. The proteins and pathways identified in these studies may represent a basis for developing new anti-HIV therapeutic strategies such as new small-molecule drugs preventing infection of CD4+ cells and viral replication, effective vaccines, "shock and kill" and "block and lock" approaches to cure latent infection.

scholarly journals Priority Intervention Targets Identified Using an In-Depth Sampling HIV Molecular Network in a Non-Subtype B Epidemics Area

2021 ◽  
Vol 11 ◽  
Author(s):  
Bin Zhao ◽  
Wei Song ◽  
Minghui An ◽  
Xue Dong ◽  
Xin Li ◽  
...  
Keyword(s):  
Genetic Distance ◽  
Molecular Network ◽  
Molecular Networks ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Targeted Interventions ◽  
Subtype B ◽  
Large Clusters ◽  
Hiv 1 ◽  
Epidemiological Information

Molecular network analysis based on the genetic similarity of HIV-1 is increasingly used to guide targeted interventions. Nevertheless, there is a lack of experience regarding molecular network inferences and targeted interventions in combination with epidemiological information in areas with diverse epidemic strains of HIV-1.We collected 2,173 pol sequences covering 84% of the total newly diagnosed HIV-1 infections in Shenyang city, Northeast China, between 2016 and 2018. Molecular networks were constructed using the optimized genetic distance threshold for main subtypes obtained using sensitivity analysis of plausible threshold ranges. The transmission rates (TR) of each large cluster were assessed using Bayesian analyses. Molecular clusters with the characteristics of ≥5 newly diagnosed cases in 2018, high TR, injection drug users (IDUs), and transmitted drug resistance (TDR) were defined as priority clusters. Several HIV-1 subtypes were identified, with a predominance of CRF01_AE (71.0%, 1,542/2,173), followed by CRF07_BC (18.1%, 393/2,173), subtype B (4.5%, 97/2,173), other subtypes (2.6%, 56/2,173), and unique recombinant forms (3.9%, 85/2,173). The overall optimal genetic distance thresholds for CRF01_AE and CRF07_BC were both 0.007 subs/site. For subtype B, it was 0.013 subs/site. 861 (42.4%) sequences of the top three subtypes formed 239 clusters (size: 2-77 sequences), including eight large clusters (size ≥10 sequences). All the eight large clusters had higher TR (median TR = 52.4/100 person-years) than that of the general HIV infections in Shenyang (10.9/100 person-years). A total of ten clusters including 231 individuals were determined as priority clusters for targeted intervention, including eight large clusters (five clusters with≥5 newly diagnosed cases in 2018, one cluster with IDUs, and two clusters with TDR (K103N, Q58E/V179D), one cluster with≥5 newly diagnosed cases in 2018, and one IDUs cluster. In conclusion, a comprehensive analysis combining in-depth sampling HIV-1 molecular networks construction using subtype-specific optimal genetic distance thresholds, and baseline epidemiological information can help to identify the targets of priority intervention in an area epidemic for non-subtype B.

scholarly journals gag, vif, and nef Genes Contribute to the Homologous Viral Interference Induced by a Nonproducer Human Immunodeficiency Virus Type 1 (HIV-1) Variant: Identification of Novel HIV-1-Inhibiting Viral Protein Mutants

1998 ◽  
Vol 72 (5) ◽  
pp. 4308-4319 ◽  
Author(s):  
Paola D’Aloja ◽  
Eleonora Olivetta ◽  
Roberta Bona ◽  
Filomena Nappi ◽  
Daniela Pedacchia ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Life Cycle ◽  
Human Immunodeficiency Virus Type ◽  
Viral Protein ◽  
Cd4 Cells ◽  
Viral Interference ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT We previously demonstrated that expression of the nonproducer F12-human immunodeficiency virus type 1 (HIV-1) variant induces a block in the replication of superinfecting HIV that does not depend on the down-regulation of CD4 HIV receptors. In order to individuate the gene(s) involved in F12-HIV-induced interference, vectors expressing each of the nine F12-HIV proteins were transfected in HIV-susceptible HeLa CD4 cells. Pools of cell clones stably producing each viral protein were infected with HIV-1, and virus release was measured in terms of reverse transcriptase activity in supernatants. We hereby demonstrate that HeLa CD4 cells expressing the F12-HIV gag, vif, ornef gene were resistant, to different degrees, to infection with T-cell-line-adapted HIV-1 strains. Conversely, expression of either the tat, rev, or vpu F12-HIV gene increased the rate of HIV release, and no apparent effects on HIV replication were observed in cells expressing either the F12-HIVvpr, pol, or env gene. No variation of CD4 exposure was detected in any of the uninfected HeLa CD4 pools. These data indicate that F12-HIV homologous viral interference is the consequence of the synergistic anti-HIV effects of Gag, Vif, and Nef proteins. Retrovirus vectors expressing F12-HIV vif ornef allowed us to further establish that the expression of each mutated protein (i) inhibits the replication of clinical HIV-1 isolates as well, (ii) impairs the infectivity of the virus released by cells chronically infected with HIV-1, and (iii) limitedly to F12-HIV Vif protein, induces HIV resistance in both vif-permissive and vif-nonpermissive cells. The levels of action of F12-HIV vif and nef anti-HIV effects were also determined. We observed that HIV virions emerging from the first viral cycle on F12-HIV vif-expressing cells, although released in unaltered amounts, had a strongly reduced ability to initiate the retrotranscription process when they reinfected parental HeLa CD4 cells. Differently, we observed that expression of F12-HIV Nef protein affects the HIV life cycle at the level of viral assembling and/or release. For the first time, an inhibitory effect on the HIV life cycle in both acutely and chronically infected cells induced by mutated Vif and Nef HIV-1 proteins is described. These genes could thus be proposed as new useful reagents for anti-HIV gene therapy.

Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China

2020 ◽  
Vol 18 (3) ◽  
pp. 210-218
Author(s):  
Guolong Yu ◽  
Yan Li ◽  
Xuhe Huang ◽  
Pingping Zhou ◽  
Jin Yan ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Phylogenetic Analyses ◽  
Resistance Mutations ◽  
Protease Inhibition ◽  
Subtype B ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

Molecular and genetic characterization of natural variants of HIV-1 Nef gene from North India and its functional implication in down-regulation of MHC-I and CD-4

2020 ◽  
Vol 18 ◽  
Author(s):  
J. Singh ◽  
L. Ronsard ◽  
M. Pandey ◽  
R. Kapoor ◽  
V.G. Ramachandran ◽  
...  
Keyword(s):  
Biological Activities ◽  
Sequence Similarity ◽  
Eukaryotic Expression ◽  
North India ◽  
Cell Surface Expression ◽  
Functional Domains ◽  
Wild Type ◽  
Down Regulation ◽  
Subtype B ◽  
Hiv 1

Background: HIV-1 Nef is an important accessory protein with multiple effector functions. Genetic studies of HIV-1 Nef gene shows extensive genetic diversity and the functional studies have been carried out mostly with Nef derived from regions dominated by subtype B (North America & Europe). Objective: This study was carried out to characterize genetic variations of the Nef gene from HIV-1 infected individuals from North-India and to find out their functional implications. Methods: The unique representative variants were sub-cloned in eukaryotic expression vector and further characterized with respect to their ability to down regulate cell surface expression of CD4 and MHC-1molecules. Results: The phylogenetic analysis of Nef variants revealed sequence similarity with either consensus subtype B or B/C recombinants. Boot scan analysis of some of our variants showed homology to B/C recombinant and some to wild type Nef B. Extensive variations were observed in most of the variants. The dN/dS ratio revealed 80% purifying selection and 20% diversifying selection implying the importance of mutations in Nef variants. Intracellular stability of Nef variants differed greatly when compared with wild type Nef B and C. There were some variants that possessed mutations in the functional domains of Nef and responsible for its differential CD4 and MHC-1 down regulation activity. Conclusion: We observed enhanced biological activities in some of the variants, perhaps arising out of amino acid substitutions in their functional domains. The CD4 and MHC-1 down-regulation activity of Nef is likely to confer immense survival advantage allowing the most rare genotype in a population to become the most abundant after a single selection event.

022 A heterosexual outbreak in Doncaster involving subtype B of HIV-1: molecular epidemiology as a supplement to contact tracing

HIV Medicine ◽  
2000 ◽  
Vol 1 (3) ◽  
pp. 172-172
Author(s):  
A Hayman ◽  
T Moss ◽  
C Arnold ◽  
l Naylor-Adamson ◽  
J Hawkswell ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Contact Tracing ◽  
Subtype B ◽  
Hiv 1

scholarly journals A Detailed Catalogue of Multi-Omics Methodologies for Identification of Putative Biomarkers and Causal Molecular Networks in Translational Cancer Research

2021 ◽  
Vol 22 (6) ◽  
pp. 2822
Author(s):  
Efstathios Iason Vlachavas ◽  
Jonas Bohn ◽  
Frank Ückert ◽  
Sylvia Nürnberg
Keyword(s):  
Cancer Research ◽  
Clinical Information ◽  
Disease Diagnosis ◽  
Molecular Data ◽  
Molecular Networks ◽  
Biological Knowledge ◽  
Omics Data ◽  
Translational Cancer Research ◽  
Using Data ◽  
Biological Entities

Recent advances in sequencing and biotechnological methodologies have led to the generation of large volumes of molecular data of different omics layers, such as genomics, transcriptomics, proteomics and metabolomics. Integration of these data with clinical information provides new opportunities to discover how perturbations in biological processes lead to disease. Using data-driven approaches for the integration and interpretation of multi-omics data could stably identify links between structural and functional information and propose causal molecular networks with potential impact on cancer pathophysiology. This knowledge can then be used to improve disease diagnosis, prognosis, prevention, and therapy. This review will summarize and categorize the most current computational methodologies and tools for integration of distinct molecular layers in the context of translational cancer research and personalized therapy. Additionally, the bioinformatics tools Multi-Omics Factor Analysis (MOFA) and netDX will be tested using omics data from public cancer resources, to assess their overall robustness, provide reproducible workflows for gaining biological knowledge from multi-omics data, and to comprehensively understand the significantly perturbed biological entities in distinct cancer types. We show that the performed supervised and unsupervised analyses result in meaningful and novel findings.

scholarly journals Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Stefania Dispinseri ◽  
Mariangela Cavarelli ◽  
Monica Tolazzi ◽  
Anna Maria Plebani ◽  
Marianne Jansson ◽  
...  
Keyword(s):  
Disease Progression ◽  
Antibody Responses ◽  
Viral Escape ◽  
Target Cells ◽  
Transmitted Virus ◽  
Slow Progressors ◽  
Vaccine Antigens ◽  
Kinetics Of ◽  
Hiv 1

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.

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